The overall objective of ttie UCSD TREC Center is to assemble transdisciplinary scientific collaborators to address questions regarding insulin resistance and inflammation underlying the association of energetics with breast cancer carcinogenesis, from the celi to the community. In Project 1, we will use obese mouse models to investigate whether the beneficial anti-inflammatory and insulin-sensitizing effects of u)3 fatty acids will reduce breast tumor growth and metastasis and whether the w3 fatty acid receptor GPR120 is the critical mediator of those cancer-protective effects. In Project 2, we will conduct a triai in obese women to examine differential response (depending on insuiin resistance status) to dietary macronutrient composition. Outcomes will include weight loss, hormonal factors, and markers of inflammation as well as nutrient-gene interactions associated with polymorphisms in IL-6 and TNF-a genes. Project 3 will investigate the degree to which metformin, a lifestyle intervention, or both, can reduce breast cancer mortality among ovenweight/obese, postmenopausal breast cancer survivors. We will use an innovative Biomarker Bridge design that links clinical outcomes from a breast cancer survivor cohort with intermediate outcomes from a randomized controlled trial. Project 4 will advance the science of energy expenditure estimation by using branched equation modeling techniques and artificial neural networks to analyze accelerometer and heart rate data from participants in Projects 2 and 3. Global Positioning System data, which track individuals' spatial-temporal paths, combined with existing Geographic Information Systems data for San Diego County, will allow us to develop obesogenic environmental exposure estimates and relate these to metabolic risk factors. Dr. Patterson, the PI forthis proposed Center, has considerable research experience in nutrition and breast cancer prevention and a strong background in leadership and management in academia and industry. The central leadership entity ofthe UCSD TREC Center will be the Executive Scientific Committee, composed of Project and Core leaders. This Committee, assisted by the Administrative Core, will provide scientific and operational oversight of the Shared Resources (Biostatistics &Bioinformatics and Biorepository) as well as the transdisciplinary Training Program and the Developmental and cross-TREC Pilot Project Core. We believe that the TREC Center proposed herein has the potential to make significant contributions to understanding the link between obesity and breast cancer and provide insight regarding interventions with broad population impact for prevention and control of disease.